Plasma levels of histamine and bradykinin reach exceedingly high levels during circulatory shock and certain anaphylactic states, yet there is no evidence for extensive extravascular fluid accumulation in skin and skeletal muscle under these conditions. This is perplexing since the local administration of bradykinin and histamine into skin and skeletal muscle vasculature promotes massive edema formation. The aim of this project is to explain these apparently contradictory observations. Preliminary data demonstrate that in contrast to local infusions of histamine and bradykinin, systemic administration of these agents promotes extravascular fluid reabsorption in skin and skeletal muscle. The data further demonstrate that this route dependent differential action of histamine and bradykinin on fluid filtration cannot be explained by differences in blood concentrations or destruction of these agents in the blood concentrations or destruction of these agents in the blood or lungs, but rather that it must be related to other as yet unidentified factors. Thus, attempts will be made to elucidate the mechanism(s) of the route dependent differential actions of histamine and bradykinin on fluid filtration. These data may have relevance to various pathophysiological states associated with high plasma levels of histamine and bradykinin. BIBLIOGRAPHIC REFERENCES: F.J. Haddy, J.B.Scott, and C.J. Grega. Peripheral Circulation: Fluid transfer across the microvascular membrane. In: International Review of Physiology, Cardiovascular Physiology II, Volume 9, edited by A.C. Guyton and A.W. Cowley, pp. 63-109, 1976. Univ. Park Press, Baltimore.